Omicron US strains: as of July 29th data - variants make up: BA.4 is 13%, BA.5 is 82%, and B2.12.1 is 5%. This Covid wave is inline with volumes from wave three which was delta. BA.5 is taking over as the new strain with excellent immune evading and vaccine evading skills. Every other strain is fading fast.

BA.5 is showing no signs of increased disease morbidity.

R0 infectiousness is in the range of measles: the new reproductive rate is 1 infects 12 which infects 144 which infects 1,728 which infects 20,736 which infects 248,832. That is a very very fast spread rate.

Little else to report here. (CDC Variants)

This week I want to add a special focus to natural immunity versus vaccine induced. Before I go there, I am NOT saying that vaccines were not incredibly useful against the Covid pandemic and they did absolutely save countless lives. Vaccines remain a very important part of the future fight against Covid. However, the booster story remains solidly in the corner of the at risk and not the rest based on many factors discussed here recently. What I am now interested in discussing is the reality that natural infection and boosting are vastly different ways to deal with the remainder of the human coexistence with SARS2.

One major difference between intramuscular vaccination and a natural infection is the development of nasal mucosal antibodies which does not generally occur following vaccination. As SARS2 is a respiratory virus, the more the naturally derived SARS2 specific antibody presence around the portal of viral entry the reduced disease risk overall. The current mRNA vaccine induced antibody response is in the serum of the blood which means that the virus has to reach the blood to activate the antibody to attack. This is much farther down the infectious process delaying viral killing at the innate immune level. Newer intranasal vaccines being looked at could bypass this issue.

"The rationale for the early mucosal immune responses against SARS-CoV-2 starts with its entry and early replication in upper airway mucosal surfaces, especially the nasopharynx. Upper airway antigenic priming gives rise to a dynamic, compartmentalized regional immune network, based on an interactive specific mucosal immune (innate and adaptive) response in nasopharyngeal-associated lymphoid tissue (NALT) inductive site, and subsequently in remote effector sites. These include the tracheobronchial epithelium, regional lymph nodes and nearby secretory glands (i.e., salivary, lacrimal or lactating mammary glands). NALT is itself a compartment of organized mucosa-associated lymphoid tissue (MALT), which is by far the largest component of the entire immune system." "Critical components of the airway mucosal immunity network which play a key role in fighting SARS-CoV-2 include mucosal immunoglobulins (Igs) - especially secretory IgA (S-IgA) - and tissue-resident memory (TRM) T and B cells as components of local adaptive immunity, and mucosa-associated invariant T (MAIT) cells, mucosal complement activation and mucosal interferons (IFNs), as components of local innate immunity." (Matuchansky et. al. 2021)

Natural infection provides a much better route to transmission protection than intramuscular systemic vaccination because of the induction of mucosal immunity via IgA and tissue resident T cells. (Tang et. al. 2022) If you can tolerate a natural infection without much morbidity, this seems to be a reasonable choice at this time. This is especially important now with the immune escaping variants of Omicron lineage and the reality of the current vaccine booster pool is lackluster in its effect on transmission. This calculus may change dramatically with a newer Omicron BA.5 specific vaccine that is in the works. In a few weeks, I am going to sit down with Dr. Paul Offit to discuss these issues further. Stay tuned!

Quick Hits and other musings -

1) Protection of natural infection against reinfection wanes and may diminish within a few years. Viral immune evasion accelerates this waning. Protection against severe reinfection remains very strong, with no evidence for waning, irrespective of variant, for over 14 months after primary infection. (Chemaitelly et. al. 2022) These data sets were with pre omicron variants thus making generalizability to today difficult. However, the protection against severe disease appears to be very solid in the Omicron arena.

2) In this study, compared with administration of COVID-19 mRNA booster vaccines alone, simultaneous administration of COVID-19 mRNA booster and seasonal influenza vaccines was associated with significant increases in reports of systemic reactions during days 0 to 7 following vaccination. These results may help better characterize the outcomes associated with simultaneously administered COVID-19 booster and influenza vaccines in the US population. (Hause et. al. 2022) The data showed that combined vaccines were more irritating to the vaccinee than the mRNA vaccine alone. The symptoms were very similar to those following dose #2 of the mRNA vaccines including myalgias, arthralgias, headache, fever and fatigue.

3) In a really thoughtful article in the NYTimes, there are more discussions on gain of function mutation research that remains ongoing by Dr. Eloit in Paris in a BSL3 biosafety lab. They have been trying to force a Furin cleavage site into a cousin of SARS2. So far so unsuccessful. Some are using this as proof that the lab leak theory is dead. Others, not so much. The debate continues. Either way many people vigorously disagree with this form of research as it could spur another pandemic. (Zimmer C. 2022)

Along this same thought process, new reports have come out related to the Wuhan animal market as a possible ground zero for the pandemic. "On 31 December 2019, the Chinese government notified the World Health Organization (WHO) of an outbreak of severe pneumonia of unknown etiology in Wuhan, Hubei province, a city of approximately 11 million people. Of the initial 41 people hospitalized with unknown pneumonia by 2 January 2020, 27 (66%) had direct exposure to the Huanan Wholesale Seafood Market (hereafter, “Huanan market”) "(Worobey et al 2022)

I am still yet unconvinced that this whole mess did not start in the BSL4 lab that is right around the corner where they happened to be working on the specific gain of function mutations for the virus. If you go to google maps, the location of the Wuhan Institute of Virology and the Huanan Market are a few blocks away and across the Yangtzee river. Coincidence? Who knows?

It doesn't really matter anymore, just interesting. For more on this topic, the Podcast with Katherine Eban and Peter Attia is really solid.

4) An important study looking at the cause of the nervous system damage again points back to the immune system overreacting to the virus leading to lots of pathology. From the Journal Brain: "All patients had multifocal vascular damage as determined by leakage of serum proteins into the brain parenchyma. This was accompanied by widespread endothelial cell activation. Platelet aggregates and microthrombi were found adherent to the endothelial cells along vascular lumina. Immune complexes with activation of the classical complement pathway were found on the endothelial cells and platelets. Perivascular infiltrates consisted of predominantly macrophages and some CD8+ T cells. Only rare CD4+ T cells and CD20+ B cells were present. Astrogliosis was also prominent in the perivascular regions. Microglial nodules were predominant in the hindbrain, which were associated with focal neuronal loss and neuronophagia. Antibody-mediated cytotoxicity directed against the endothelial cells is the most likely initiating event that leads to vascular leakage, platelet aggregation, neuroinflammation and neuronal injury. Therapeutic modalities directed against immune complexes should be considered." (Lee et. al. 2022)

Also, from Med RxIV we see that a study led by Dr. Visser noted profound neuroinflammation in patients with PACS. (Visser et. al. 2022) These studies are all likely going to be tied together.

Inflammation and vascular leak are at the center of the damage that we see as brain chronic brain fog, headache, anosmia and all of the other brain related pathology following Covid.

5) Could genetics be the key to not having to battle Covid yearly? Nope. So far the research is showing that everyone is susceptible to the SARS2 viral illness with a very wide range of infection symptomatology. Unlike HIV and malaria where there are known genetic mutations that make the host resistant to the infection, SARS2 does not appear to be in the same category. However, it is clear that there is a large subset of people that get minor to no symptoms despite being infected and this is likely a combination of genetics and baseline health.

This is very important

6) From JAMA: "Among 902 study participants, 697 had confirmed SARS-CoV-2 infection, including 351 children or older siblings and 346 parents. Among 697 cases, 674 (96.7%) were asymptomatic or mild. Children had significantly higher S-RBD IgG titers than older patients across all follow-up time points, with an overall median S-RBD IgG titer in patients younger than 3 years 5-fold higher than adults. Longitudinal analysis of 56 study participants sampled at least twice during follow-up demonstrated the persistence of antibodies up to 10 months from infection in all age classes, despite a progressive decline over time." (Chiara et. al. 2022)

Children fare much better with SARS2 and have demonstrated much better immune T and B cell activity across many epitopes post natural infection than adults. They hold their long term immunity well and almost all children are minimally symptomatic with reinfection. This begs the question of any vaccination need in this previously infected group moving forward unless we have the ability to really stem transmission. The main thrust of information remains that as a society we should be promoting immune and gut health through diet, sleep and stress reduction as discussed often here. That is the true route of health over time.

7) Increased blood volume in Covid hospitalized patients is associated with mortality. (Choi et. al. 2022) The reasoning here is because the virus is triggering the innate immune system to inflame close to the local tissue wherever the virus is found. The secondary consequence of which is recruitment of cells to the area which include white and red blood cells. These cells raise blood viscosity volumetrically which appears systemically over time. This is a test that could help predict worse outcomes in hospitalized patients.

8) From Scientific American: "SARS-CoV-2, though, may have come up with an ingenious work-around. It may completely do away with the molecular maneuverings needed to attach to and unlock a cell membrane. Instead it wields a blunt instrument in the form of nanotube “bridges”—cylinders constructed of the common protein actin that are no more than a few tens of nanometers in diameter. These tunneling nanotubes extend across cell-to-cell gaps to penetrate a neighbor and give viral particles a direct route into COVID-impervious tissue." (Pappas S. 2022) This is some truly incredible discovery. Working in the 10 to the minus 9th size is so remarkable for understanding let alone the fact that the virus can engineer these nanotubes to travel through. Nature is AMAZING!

9) In a new study from the British Medical Journal, the meta analysis noted that roughly 5+% of patients having had covid continued to have smell and taste dysfunction that shows no signs of returning to normal. (Tan et. al. 2022) This is an unfortunate burden for these individuals as smell and taste are 2 of the 5 primary senses that help us navigate the world of food, toxins, danger etc.... Being able to smell or taste spoiled food, gas leaks and other dangerous situations is critical.

That's all this week,

Dr. M

Matuchansky Clin Microb Infect

Tang Science Immunology

Matuchansky NEJM

Chemaitelly MedRxIV

Hause JAMA

Zimmer NYTimes

Worobey Science

Lee Brain

Visser MedRxIV

Wu Atlantic

Chiara JAMA

Choi J Amer College Card

Pappas Scientific American

Tan BMJ

CDC MMWR

CDC Variants Page

CDC Covid Deaths

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